Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma (HCC), but with limited efficacy. The present study aimed to prospectively investigate the efficacy and analyze the prognostic factors for survival in sorafenib-treated patients with advanced HCC. The baseline characteristics and clinical outcomes of 110 patients with advanced hepatitis B virus-related HCC treated with sorafenib with/without local therapy (transarterial chemoembolization with/without cryoablation) at a single liver cancer center were recorded. Predictors of progression-free survival (PFS) and overall survival (OS) were determined by multivariate analysis. A total of 14 (12.7%) patients achieved complete response (CR), 16 (14.5%) achieved partial response (PR) and 40 (36.4%) achieved stable disease (SD) lasting longer than 8 weeks. The median OS and PFS for the whole cohort were 10.5 [95% confidence interval (CI), 8.7-12.3] and 5.0 months (95% CI, 3.7-6.3), respectively. Sorafenib in combination with local therapy was an independent predictor for longer PFS, whereas Eastern Cooperative Group (ECOG) performance status (PS) and Child-Pugh class were associated with reduced PFS. Local therapy was associated with longer OS while ECOG PS and α-fetoprotein were associated with reduced OS. In a subset of patients with radiological progressive disease, a significant difference was found in OS between patients who continued taking sorafenib and those who discontinued therapy (11 vs. 7.5 months, P<0.001). In conclusion, sorafenib in combination with local therapy (transarterial chemoembolization with/without cryoablation) was independently associated with longer OS and PFS in advanced HCC patients. Poor ECOG PS was associated with shorter OS and PFS and is thus a marker of poor outcomes in sorafenib-treated HCC patients.